The purposes of this research program are to determine the inter-relationship of glucose stimulation of insulin release and other insulin secretagogues on the acute uptake and efflux of 45Ca from isolated rat islets; determine the binding properties to subcellular fractions of the islets; determine the subcellular distribution of calcium in isolated islets; determine the effect of glucose and other agents on the uptake and efflux of zinc in isolated rat islets. The uptake and efflux of 45Ca by isolated islets is determined by the dual-label isotope technique. Studies have been completed on the acute effect of D-glucose on the uptake and efflux of 45Ca in the presence and absence of insulin release and studies are to be accomplished on the effect of alpha and beta anomers of D-glucose, tolbutamide, arginine, leucine, dibutyryl cyclic AMP, theophylline, alloxan, and cytochalasins B and D on the uptake and efflux of 45Ca. A digestion filtration technique has been developed for the mass isolation of rat islets and this procedure will be used to study the binding of 45Ca to membrane fractions of the islets and the subcellular distribution of 45Ca following glucose stimulation. 65Zinc metabolism in isolated rat islets will be determined with the dual-label isotope technique. The pattern, rate and amount of 65Zn uptake and efflux from isolated islets will be determined following stimulation with insulin secretagogues in the presence and absence of insulin release. BIBLIOGRAPHIC REFERENCES: Shibata, A., Ludvigsen, C., Naber, S.P., McDaniel, M.L. and Lacy, P.E.: Standardization of a Digestion-Filtration Method for Isolation of Pancreatic Islets. Diabetes, 1976. In Press. Naber, S.P., McDaniel, M.L. and Lacy, P.E.: Calcium-45 Movements in Isolated Islets: Effect of Glucose and D2O. Abstract, American Diabetes Association Meeting, June, 1976.